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Background: The hippocampus is a critical brain structure for memory formation and other aspects of cognition. The hippocampus and the white matter tracts connecting it to other parts of the brain are known to lose volume and integrity with aging. For populations with prior compromised hippocampal integrity, such as those

Background: The hippocampus is a critical brain structure for memory formation and other aspects of cognition. The hippocampus and the white matter tracts connecting it to other parts of the brain are known to lose volume and integrity with aging. For populations with prior compromised hippocampal integrity, such as those with autism spectrum disorder (ASD), it is less well known how the hippocampus and its connections will respond to aging. In children with ASD, there may be an initial period of enlarged hippocampi, after which there is a trajectory of faster decline in volume compared to neurotypicals (NT). We have previously identified reduced hippocampal volumes and fornix white matter integrity in middle-age and older adults with ASD compared to matched NT adults. However, freewater (FW) may be a more sensitive structural integrity measure of the hippocampal complex. FW is present in the brain as cerebrospinal fluid but also accumulates within the extracellular spaces indicative of reduced gray matter density and increased axon degeneration. FW shows promise as a more sensitive biomarker for Parkinson’s and Alzheimer’s disease. This study evaluated age-related hippocampal complex FW differences in adults with and without ASD across the adult lifespan. We hypothesized that adults with ASD would demonstrate a larger age association with increasing FW in the hippocampus and fornix, compared to NT adults, and that FW would be a more sensitive brain measure than traditional fractional anisotropy (FA).

Methods: The study consisted of 79 participants with ASD (59 male, 20 female; ages 18-70, mean=40.27 [±17] years) and 77 NT participants (46 male, 31 female; ages 18-71, mean=40.33 [±16] years). Hippocampal and fornix FW and FA values were generated from diffusion tensor images obtained along 32 directions using a b-value of 2500 s/mm2 in the axial direction with 3 mm slice resolution. These images were then processed for eddy current, distortion, b-vec and motion correction, skull stripped, and non-linear registered using Advanced Normalization Tools (ANTs) to the subject’s T1 image. FW and FA maps were calculated using custom written MatLab code and standard atlases containing the hippocampus and fornix were applied.

Results: The right hippocampus showed a significant diagnosis by age interaction (p=0.018), such that the increase in FW with age was greater for adults with ASD. The left hippocampus diagnosis by age interaction approached significance (p=0.055). Similarly, the right fornix showed a significant diagnosis by age interaction (p=0.044), with increases in FW with age as greater for adults with ASD, and the left fornix diagnosis by age interaction approached significance (p=0.053). FA values showed no significant diagnosis by age interactions.

Conclusion: In the hippocampus and fornix, the association between increasing FW and increasing age was more pronounced for adults with ASD than matched NT adults. This may mean that as adults with ASD age, these regions will degenerate faster than their NT peers, which could have implications for accelerated age-related memory decline. However, a notable limitation is the cross-sectional nature of the study. Our ongoing longitudinal study will inform a more definitive picture of brain aging with ASD.
ContributorsAlvar, Jocelyn R (Author) / Braden, Brittany Blair (Thesis director) / Ofori, Edward (Committee member) / School of Life Sciences (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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The gastrointestinal (GI) tract is home to a complex and diverse microbial ecosystem that contributes to health or disease in many aspects. While bacterial species are the majority in the GI tract, their cohabitants, fungal species, should not be forgotten. Children with autism spectrum disorder (ASD) often suffer from GI

The gastrointestinal (GI) tract is home to a complex and diverse microbial ecosystem that contributes to health or disease in many aspects. While bacterial species are the majority in the GI tract, their cohabitants, fungal species, should not be forgotten. Children with autism spectrum disorder (ASD) often suffer from GI disorders and associated symptoms, implying a role the bacterial and fungal gut microbiota play in maintaining human health. The irregularities in GI symptoms can negatively affect the overall quality of life or even worsen behavioral symptoms the children present. Even with the increase in the availability of next-generation sequencing technologies, the composition and diversities of fungal microbiotas are understudied, especially in the context of ASD. We therefore aimed to investigate the gut mycobiota of 36 neurotypical children and 38 children with ASD. We obtained stool samples from all participants, as well as autism severity and GI symptom scores to help us understand the effect the mycobiome has on these symptoms. By targeting the fungal internal transcribed spacer (ITS) and bacterial 16S rRNA V4 regions, we obtained fungal and bacterial amplicon sequences, from which we investigated the diversities, composition, and potential link between two different ecological clades. From fungal amplicon sequencing results, we observed a significant decrease in the observed fungal OTUs in children with ASD, implying a lack of potentially beneficial fungi in ASD subjects. We performed Bray-Curtis principal coordinates analysis and observed significant differences in fungal microbiota composition between the two groups. Taxonomic analysis showed higher relative abundances of Candida , Pichia, Penicillium , and Exophiala in ASD subjects, yet due to a large dispersion of data, the differences were not statistically significant. Interestingly, we observed a bimodal distribution of Candida abundances within children with ASD. Candida's relative abundance was not significantly correlated with GI scores, but children with high Candida relative abundances presented significantly higher Autism Treatment Evaluation Checklist (ATEC) scores, suggesting a role of Candida on ASD behavioral symptoms. Regarding the bacterial gut microbiota, we found marginally lower observed OTUs and significantly lower relative abundance of Prevotella in the ASD group, which was consistent with previous studies. Taken together, we demonstrated that autism is closely linked with a distinct gut mycobiota, characterized by a loss of fungal and bacterial diversity and an altered fungal and bacterial composition.
ContributorsPatel, Jigar (Author) / Krajmalnik-Brown, Rosa (Thesis director) / Kang, Dae Wook (Committee member) / Adams, James (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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The purpose of this project was to develop a new questionnaire that was comprehensive and included symptoms of autism and related disorders. 28 parents of children with autism and two adults with autism were interviewed and asked to fill out the questionnaire and rate their child’s symptoms based on the

The purpose of this project was to develop a new questionnaire that was comprehensive and included symptoms of autism and related disorders. 28 parents of children with autism and two adults with autism were interviewed and asked to fill out the questionnaire and rate their child’s symptoms based on the available scale. From their responses, we were able to edit and improve the questionnaire to make it clearer and more concise. We added new symptoms and improved the descriptions of the symptoms listed. The new version of the questionnaire will be edited after interviewing the same 30 people again. After, it will need to be validated by a large study of around 300 people. The questionnaire will be used in an app format and help parents rate their child’s symptoms during clinical studies of medical treatments.

ContributorsFoote, Sophia (Author) / Adams, James (Thesis director) / Duane, Drake (Committee member) / Barrett, The Honors College (Contributor) / Watts College of Public Service & Community Solut (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2022-05
Description
For my thesis I investigated an abnormal gut-derived metabolite of interest identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) that may serve as a potential biomarker for autism, and help us get a better understanding of the underlying mechanisms of this disorder. Currently a laboratory test for autism does not exist, posing severe

For my thesis I investigated an abnormal gut-derived metabolite of interest identified as 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA) that may serve as a potential biomarker for autism, and help us get a better understanding of the underlying mechanisms of this disorder. Currently a laboratory test for autism does not exist, posing severe consequences on individuals with autism. In order to gather research on my metabolite of interest and its connection to autism as well as disorders correlated with autism, I analyzed different pieces of scientific literature investigating HPHPA and compiled this data into a literature review.
ContributorsNawaz, Umar (Author) / Adams, James (Thesis director) / Krajmalnik-Brown, Rosa (Committee member) / Flynn, Christina (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2024-05
Description
Autism Spectrum Disorder (ASD) is an intricate neurodevelopmental disorder characterized by impaired social functioning and communication, repetitive behavioral patterns, and specialized interests (Olesova et al., 2020; Osredkar et al., 2023). Despite the efforts of modern science, the biological origin of ASD is unknown, and no known biomarker for ASD currently

Autism Spectrum Disorder (ASD) is an intricate neurodevelopmental disorder characterized by impaired social functioning and communication, repetitive behavioral patterns, and specialized interests (Olesova et al., 2020; Osredkar et al., 2023). Despite the efforts of modern science, the biological origin of ASD is unknown, and no known biomarker for ASD currently exists (Olesova et al., 2020; Osredkar et al., 2023). Indoxyl sulfate has been identified as a toxin associated with ASD and its related symptomology in addition to a number of other conditions, including chronic kidney disease, acute kidney injury, heart failure, Parkinson’s disease, and various mood disorders (Cao et al., 2015; Cassani et al., 2015; Karbowska et al., 2020; Zhao et al., 2013). This article will review what is currently known about indoxyl sulfate in relation to ASD and its comorbidities in an attempt to determine the validity of indoxyl sulfate as a potential biomarker for ASD. Articles for the purposes of this review were collected via Google Scholar, PubMed, and the ASU Library using key words such as “indoxyl sulfate,” “Autism,” and “indican,” and chosen based on relevancy. Through this review, indoxyl sulfate was identified as a potential physiological biomarker for a subset of ASD, with additional research required to verify the findings presented. The identification of a biomarker for ASD could change the current methods of testing for ASD, greatly improving our understanding and treatment of the disorder.
ContributorsHill, Zoë (Author) / Adams, James (Thesis director) / Flynn, Christina (Committee member) / Barrett, The Honors College (Contributor) / College of Health Solutions (Contributor) / Edson College of Nursing and Health Innovation (Contributor)
Created2024-05
Description

Introduction: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder that increased in prevalence in the last few decades, most notably among older adults. The gap in knowledge of aging processes, among individuals with ASD, and the increasing prevalence of Parkinsonism diagnosis in this population, revealed a need for research

Introduction: Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental disorder that increased in prevalence in the last few decades, most notably among older adults. The gap in knowledge of aging processes, among individuals with ASD, and the increasing prevalence of Parkinsonism diagnosis in this population, revealed a need for research efforts. Nevertheless, differences in the group and age-related differences in cortical thickness in brain regions associated with motor control remain relatively unexplored. Objective: In this study, we analyzed cross-sectional data to investigate group differences and age-related differences in cortical thickness of the left hemisphere (lh) and right hemisphere (rh) of the precentral gyrus and paracentral lobule, in adults with ASD vs. NT adults. Knowing that individuals with ASD present greater group and age-related motor impairments than NT individuals, we tested the following hypothesis: adults with ASD will demonstrate reduced cortical thickness and greater relationships between increasing age and decreasing cortical thickness in the precentral gyrus and paracentral lobule than the NT participants. Methods: Group and age-related differences in cortical thickness were analyzed in our cohort of 191 participants with (N=105; ages 18-71) and without ASD (N=86 ages 18-70). T1-weighted MRI images were collected from each participant and were analyzed using FreeSurfer to obtain cortical thickness measurements from the motor regions of interest. Using SPSS (IBM SPSS Statistics for macOs, Version 28.0.1.1) univariate general linear models were used to test the between-subject effects of group, age, and group by age interaction, with sex as a covariate. Results: A statistically significant effect of the diagnosis group on cortical thickness was only observed in the lh precentral gyrus, with the ASD group showing a thinner cortex than the NT group. A statistically significant group-by-age interaction was present in the cortical thickness of the lh precentral gyrus, the rh precentral gyrus, and the lh paracentral lobule. For each interaction, the relationship between age and cortical thickness had a steeper negative slope in the ASD group compared to the NT group. Discussion: Consistent with our hypothesis, findings indicate ASD affects cortical thickness and may be linked to greater age-related reduced cortical thickness, of the studied motor areas, in adults with ASD compared to NT adults. Future research is warranted to investigate the relationship between cortical thickness in motor regions and the severity of motor impairments in the ASD population. Further longitudinal investigations of the age-related changes (trajectories) in cortical thickness, specific to motor regions, in individuals with ASD, are also necessary.

ContributorsValdez, Melony (Author) / Braden, Brittany (Thesis director) / Ofori, Edward (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05